IMMUNOLOGY/IMMUNOTHERAPY (IMM) ? PROJECT SUMMARY/ABSTRACT The immune system is an important means to control cancer. It is also the source of hematologic malignancies. The goals of the Immunology/Immunotherapy (IMM) Program are to support basic, translational, and clinical research to improve the immune response to cancer, and to translate understanding of hematopoietic cell development into treatment of hematologic malignancies. These goals are encompassed in 3 Specific Aims: 1. to develop and optimize the efficacy of antigen-specific immunotherapeutics; 2. to understand and modulate T cell function and regulation in the tumor microenvironment; 3. to understand normal pathways of hematopoietic cell development and their dysregulation in human hematologic malignancies. Each aim includes outstanding basic science investigations, and highly collaborative translational initiatives and clinical trials. The Program co-leaders are internationally recognized for their work in tumor antigen identification, induction of tumor-specific CD8 T cell responses, and cancer immunotherapy clinical trials. The Program consists of 30 members and 7 associate members from 9 departments/divisions in the School of Medicine. Total extramural funding is over $11.17M, including over $4.04M from the NCI and over $4.77M from other NIH institutes. Program members have published 216 papers over the last 5 years, of which 12% were inter-programmatic and 16% were intraprogrammatic. The Program supports research in progress presentations and seminars to engender new directions and collaborations; pilot funding to encourage development of promising collaborations and ideas; and an Immune Monitoring Laboratory to facilitate clinical research. Seventeen clinical trials led by Program members are open to enrollment across 5 cancer histologies (pancreatic cancer, breast cancer, head and neck cancer, prostate cancer, and melanoma). They include 10 investigator-initiated trials, of which three are multicenter. These trials are evaluating cancer vaccines, checkpoint blockade antibodies and combination immunotherapies. These trials test hypotheses arising from laboratory science and also bring tissue to the laboratories to investigate cellular processes and molecular mechanisms to explain the clinical findings. This Program provides a firm foundation for continued advances in understanding of the immune system and utilizing that knowledge to improve immunotherapy and treatment of hematologic malignancies.